RCVS – Reversible Cerebral Vasoconstriction Syndrome

 

   Segmental cerebral vasoconstriction usually associated with acute onset of severe (thunderclap) headache, reversible (within 3 months)

   Other names:

o   Call-Fleming Syndrome

o   Thunderclap headache with reversible vasospasm

o   Benign angiopathy of the CNS (BACNS)

o   Migrainous vasospasm or angiitis

o   Drug induced cerebral vasculopathy

o   The name RCVS was proposed in 2007

   Can result in PRES however is not synonymous (see PRES topic)

 

Epidemiology

   Age 10-76yr in literature

   Peak age 42

   Female >Male

   Incidence ?? no good data

   Risk factors:

o   ?History of migraine

Aetiology

   Primary causes

o   “Primary thunderclap headache”

o   Exertional headache, headache associated with cough/bathing/sexual activity

o   N.B. although these primary headaches can be associated with vasospasm often they do not appear to be and conceivably may have a variety of causes.

   Secondary causes

o   Pregnancy/Postpartum

-   Either ‘idiopathic’ or associated with eclampsia or vasoactive drugs given during pregnancy

o   Vasoactive substances

-   Illicit drugs

   Cannabis, cocaine, ecstasy, amphetamines, LSD

-   Ergots

   Ergotamine, bromocriptine, methergine

-   Sympathomimetics

   Ephedrine, pseudoephedrine, diet pills

-   Serotonergic drugs

   SSRI, SNRI, triptans

-   Immunosuppressants

   Tacrolimus, cyclophosphamide, IFN-a

-   Other

   Indomethacin, OCP, nicotine patches

   Ginseng

   Alcohol – binge

o   Catecholamine secreting tumours

-   Phaeochromocytoma

-   Bronchial carcinoid tumour

-   Glomus tumour

o   Arterial/Vascular disorders

-   Dissection

-   CEA

-   PRES

-   ?CVST, ?Aneurysm

o   Blood products

-   EPO, IVIG, massive transfusion

o   Intracranial disorders

-   ICH, trauma, intracranial hypotension, neurosurgery

o   Misc

-   Hypercalcaemia, SLE, Autonomic dysreflexia, phenytoin intoxication, porphyria

Clinical manifestations

   Thunderclap headache (Thunderclap Headache)

o   Initial symptom in >80%

o   Often can be recurrent (2-10 headaches, mean of 4) over 1- 4 weeks

o   More often posterior onset

o   Last minutes to days (usually 1-3 hours) – this is shorter than SAH

o   A moderate, ‘background’ headache can persist between attacks

   Seizures (1%-17%)

o   Recurrent seizures are rare

   Focal neurological deficits (8-43%)

o   Most often visual

   Hypertension - 1/3 patients

o   ?pain vs underlying aetiology

 

 

Diagnosis

   Major differential diagnosis is SAH for clinical presentation and vasculitis for radiological findings

o   CT +/- LP +/- CTA to exclude SAH

o   MRI brain – to look for alternative causes and complications of RCVS

o   If there is reason to suspect vasculitis investigation for this – including biopsy should be considered.

   Vascular imaging

o   The vasospasm can be delayed – up to 3 weeks (mean 16 days) to reach maximal, initial scanning can be negative

o   Segmental narrowing, ‘string of beads’

o   Modality depends on local access:

-   Catheter angiography – gold standard

-   Non-invasive

   Sensitivity of non-invasive imaging ~70%

   MRA/CTA/USS

   Transcranial doppler may be useful for monitoring progress of disease

 

   Response to intravascular nimodipine has been proposed but not proven

 

   Lumbar puncture

o   To exclude other causes

o   White cell count

-   Elevation up to 35 has been reported

-   >10 in 3-8%

-   5-10 in up to17%

o   Protein >600mg/L in up to16%

o   Has been suggested to repeat LP in a few weeks if WCC >10 or Protein >800mg/L

 

   Bloods

o   Could consider vasculitis screen

o   Consider screen for phaeochromocytoma

o   Consider Drug screen

 

   Proposed diagnostic criteria (Calabrese et al. 2007):

o   Documentation of multifocal segmental cerebral artery vasospasm

o   No evidence of aneurysmal SAH

o   Normal or near normal CSF

o   Severe, acute headaches (with or without other focal neurological signs)

o   Reversibility within 12 weeks (or significant improvement ?). If death occurs within this time-frame autopsy evidence ruling out vasculitis or other causes.

Important DDx:

   SAH – has to be excluded first in all cases of thunderclap headache

   Cerebral vasculitis

o   More insidious onset

o   Progressive symptoms

o   MRI shows infarcts on initial scan in >90% of cases

o   Inflammatory CSF in >95%

o   Vasoconstriction often not visualised

Complications

   A number of complications have been attributed to RCVS (although it could not be ruled out that some are causative rather than complications)

 

TIA

16%

 

PRES

9-14%

Usually with onset, often associated with stroke

Cerebral oedema

38%

 

ICH

up to 20%

Often occur with the thunderclap headache

Cortical/convexity SAH

22 to 34%

Half seen within first week

SDH

2%

 

Stroke

6-39%

Watershed, often between PCA/MCA, usually occur later (mean 9-10 days, reported up to 17 days)

 

Prognosis

   Permanent neurological deficits  - 3-9%

   Stroke deficits are usually relatively small

   Rarely case reports of mortality (<1%)

   Recurrence rate unknown

o   In one study (from Taiwan of 168pts) 10.7% of patients had recurrent thunderclap headache and 5.4% had proven recurrence at a mean of 41 months post initial episode. None developed complications. (Neurology 2015)

 

Treatment

   Pain relief

   Identification and elimination of exacerbating factors

   Manage complications:

o   E.g. Seizures

   Blood pressure

o   ?Manage as per acute stroke – i.e. do not aim for rapid reduction

   Treatment of vasospasm

o   Nimodipine

-   1-2mg/hr IV adapted to blood pressure then oral 30-60mg Q4H for 4-8 weeks

-   Reduced number and intensity of headaches

-   Did not change time course of vasospasm

-   Complications (TIA/Stroke/ICH) have occurred despite treatment

-   One paper suggests early treatment improves resolution – with no difference in complications (Effect of Nimodipine Treatment on the Clinical Course of Reversible Cerebral Vasoconstriction Syndrome. Front Neurol. 2019;10:644.)

o   Verapamil (case reports of ‘effectiveness’)

o   Magnesium sulphate

   Steroids

o   No proven benefit – concern about worsening.

   Intraarterial vasodilators

o   Case reports with ‘debatable success